C1q/TNF-related proteins, a family of novel adipokines, induce vascular relaxation through the adiponectin receptor-1/AMPK/eNOS/nitric oxide signaling pathway

Qijun Zheng, Yuexing Yuan, Wei Yi, Wayne Bond Lau, Yajing Wang, Xiaoliang Wang, Yang Sun, Bernard L. Lopez, Theodore A. Christopher, Jonathan M. Peterson, G. William Wong, Shiqiang Yu, Dinghua Yi, Xin Liang Ma

Research output: Contribution to journalArticle

Abstract

Objective-: Reduced plasma adiponectin (APN) in diabetic patients is associated with endothelial dysfunction. However, APN knockout animals manifest modest systemic dysfunction unless metabolically challenged. The protein family CTRPs (C1q/TNF-related proteins) has recently been identified as APN paralogs and some CTRP members share APN′s metabolic regulatory function. However, the vasoactive properties of CTRPs remain completely unknown. Methods and Results-: The vasoactivity of currently identified murine CTRP members was assessed in aortic vascular rings and underlying molecular mechanisms was elucidated in human umbilical vein endothelial cells. Of 8 CTRPs, CTRPs 3, 5, and 9 caused significant vasorelaxation. The vasoactive potency of CTRP9 exceeded that of APN (3-fold) and is endothelium-dependent and nitric oxide (NO)-mediated. Mechanistically, CTRP9 increased AMPK/Akt/eNOS phosphorylation and increased NO production. AMPK knockdown completely blocked CTRP9-induced Akt/eNOS phosphorylation and NO production. Akt knockdown had no significant effect on CTRP9-induced AMPK phosphorylation, but blocked eNOS phosphorylation and NO production. Adiponectin receptor 1, but not receptor 2, knockdown blocked CTRP9-induced AMPK/Akt/eNOS phosphorylation and NO production. Finally, preincubating vascular rings with an AMPK-inhibitor abolished CTRP9-induced vasorelaxative effects. Conclusion-: We have provided the first evidence that CTRP9 is a novel vasorelaxative adipocytokine that may exert vasculoprotective effects via the adiponectin receptor 1/AMPK/eNOS dependent/NO mediated signaling pathway.

Original languageEnglish (US)
Pages (from-to)2616-2623
Number of pages8
JournalArteriosclerosis, thrombosis, and vascular biology
Volume31
Issue number11
DOIs
StatePublished - Nov 2011

Keywords

  • diabetes mellitus
  • endothelial function
  • nitric oxide
  • signal transduction

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Zheng, Q., Yuan, Y., Yi, W., Lau, W. B., Wang, Y., Wang, X., Sun, Y., Lopez, B. L., Christopher, T. A., Peterson, J. M., Wong, G. W., Yu, S., Yi, D., & Ma, X. L. (2011). C1q/TNF-related proteins, a family of novel adipokines, induce vascular relaxation through the adiponectin receptor-1/AMPK/eNOS/nitric oxide signaling pathway. Arteriosclerosis, thrombosis, and vascular biology, 31(11), 2616-2623. https://doi.org/10.1161/ATVBAHA.111.231050